Infantile hemangiomas β3-adrenoceptor overexpression is associated with nonresponse to propranolol

Background Propranolol (antagonist of beta(1)-/beta(2)-AR but minimally active against beta(3)-AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of beta(2)-AR. However, its success rate is similar to 60%. Considering the growing interest in the angiogenic role of beta(3)-ARs, we evaluated a possible relationship between beta(3)-AR expression and response to propranolol. Methods Fifteen samples of surgical biopsies were collected from patients with IH. Three were taken precociously from infants and then successfully treated with propranolol (responder group). Twelve were taken later, from residual lesions noncompletely responsive to propranolol (nonresponder group). A morphometrical analysis of the percentage of beta(1)-, beta(2)-, and beta(3)-ARs positively stained area was compared between the two groups. Results While no difference was found in both beta(1)- and beta(2)-AR expression level, a statistically significant increase of beta(3)-AR positively stained area was observed in the nonresponder group. Conclusions Although the number of biopsies is insufficient to draw definitive conclusions, and the different beta-AR pattern may be theoretically explained by the different timing of samplings, this study suggests a possible correlation between beta(3)-AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH. Impact Propranolol (unselective antagonist of beta(1) and beta(2)-ARs) is currently the first-line treatment for IHs, with a success rate of similar to 60%. Its effectiveness has been attributed to its ability to block beta(2)-ARs. However, beta(3)-ARs (on which propranolol is minimally active) were significantly more expressed in hemangioma biopsies taken from patients nonresponsive to propranolol. This study suggests a possible role of beta(3)-ARs in hemangioma pathogenesis and a possible new therapeutic target.

Automated summary

The research found a significant increase in the expression of beta(3)-AR in hemangioma biopsies from patients nonresponsive to propranolol treatment. This suggests a possible role of beta(3)-AR in the pathogenesis of hemangiomas and a potential new therapeutic target.